DESCRIPTION: (Applicant's Abstract) Hepatitis C (HCV) and Human Immunodeficiency virus (HIV) cause chronic infections of worldwide importance. Because they share parenteral factors for transmission, over one third of patients with HIV are usually co-infected with HCV and nearly 400,000 individuals in the United States are positive for both viruses. Patients with co-infection have more aggressive liver disease and increased incidence of cirrhosis than patients with HCV only. While the reasons for this are unclear, it is possible that co-existent alcoholism in this population is at least partially responsible. Alcohol may further modulate host immune suppression and have specific effects on host immune defenses resulting in increased viral replication and mutational pressure on HCV. The overall goal of this proposal is to study and clarify the effects of alcohol on HCV and progressive liver disease in patients who are co-infected with HIV. The specific aims are: 1) We will evaluate a cohort of HCV/HIV positive patients and identify the sociodemographic, histological, and clinical variables of these individuals that are affected by excess alcohol consumption and most likely to be important for progressive liver disease. 2) We will then sequence and compare important genomic regions of HCV isolated from these patients and determine the significance of quasispecies diversity for HCV pathology. 3) We will study the effects of antiviral therapy on the composition and diversity of HCV genomic regions and determine their importance for patient prognosis and response to therapy. Our work will clarify the epidemiology, natural history, and pathology of alcohol in these patients. It will also provide an increased understanding of progressive liver disease in this population that will aid in future management and antiviral therapy.